Serine proteinase inhibitor therapy in alpha(1)-antitrypsin inhibitor deficiency and cystic fibrosis.

S Lorraine Martin, Damian Downey, Diana Bilton, Mary T Keogan, Julia Edgar, J Stuart Elborn

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29 Citations (Scopus)


Proteinase-antiproteinase imbalances are recognized in several diseases including the two most common lethal hereditary disorders of white populations, alpha(1)-antitrypsin (alpha(1)-AT) deficiency and cystic fibrosis (CF). In alpha(1)-AT deficiency, the type Z variant of alpha(1)-AT forms polymers in the endoplasmic reticulum of hepatocytes resulting in liver disease in childhood. The block in alpha(1)-AT processing in hepatocytes significantly reduces levels of circulating alpha(1)-AT. This may lead in young adults to panacinar emphysema due to insufficient protection of the lower respiratory tract from neutrophil elastase, permitting progressive destruction of the alveoli. In CF, chronic bacterial lung infections due to impaired mucociliary clearance lead to a vigorous influx of neutrophils in the airways. Released levels of neutrophil serine proteinases, particularly elastase, exceed the antiproteinase capacity of endogenous serine proteinase inhibitors in the airways. Progressive proteolytic impairment of multiple defense pathways in addition to endobronchial obstruction and airway wall destruction are thought to be responsible for the reduced life expectancy in CF patients. Strategies to augment the antiproteinase defenses in the airways of patients with severe alpha(1)-AT deficiency or CF include the intravenous or aerosol administration of serine proteinase inhibitors. Studies in both patient groups using plasma-derived or transgenic alpha(1)-AT, recombinant secretory leukoprotease inhibitor or synthetic elastase inhibitors show promising results concerning drug safety and efficacy.
Original languageEnglish
Pages (from-to)363-375
Number of pages13
JournalPediatric Pulmonology
Issue number2
Publication statusPublished - 2006


  • administration
  • adolescent
  • adult
  • aged
  • alpha 1 antitrypsin
  • alpha 1 antitrypsin administration & dosage
  • alpha 1 antitrypsin therapeutic use
  • cystic fibrosis
  • cystic fibrosis drug therapy
  • cystic fibrosis metabolism
  • cystic fibrosis physiopathology
  • double blind method
  • female
  • follow up studies
  • forced expiratory flow rates
  • forced expiratory flow rates physiology
  • humans
  • inhalation
  • leukocyte elastase
  • leukocyte elastase metabolism
  • male
  • middle aged
  • nebulizers vaporizers
  • pilot projects
  • recombinant proteins
  • recombinant proteins administration & dosage
  • recombinant proteins therapeutic use
  • serine proteinase inhibitors
  • serine proteinase inhibitors administration & dos
  • serine proteinase inhibitors therapeutic use
  • sputum
  • sputum metabolism
  • treatment outcome


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